Histological Prostatic Inflammation Is Associated With Storage Lower Urinary Tract Symptoms and Inflammatory/Fibrotic Marker Expression in Benign Prostate Biopsies

Abstract

ABSTRACT Background Chronic histological inflammation is frequently observed in benign prostate tissue; however, its clinical significance and biological relationship with lower urinary tract symptoms (LUTS) remain incompletely understood. We investigated whether histological inflammation identified in benign prostate biopsy specimens is associated with symptom severity, inflammatory cytokine expression, and tissue microstructural changes. Methods This retrospective study included 123 men who underwent transperineal prostate biopsy because of elevated prostate‐specific antigen levels and/or suspicious magnetic resonance imaging findings and were subsequently confirmed to have no histological evidence of malignancy. Histological inflammation was graded using a modified Nickel classification system and correlated with clinical parameters, including the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI), and International Index of Erectile Function‐5 (IIEF‐5). Immunohistochemical expression of cyclooxygenase‐2 (COX‐2), interleukin‐6 (IL‐6), and transforming growth factor‐β (TGF‐β) was assessed in representative specimens. Apparent diffusion coefficient (ADC) values derived from diffusion‐weighted MRI were evaluated in an exploratory analysis. Results Histological inflammation was identified in 91.1% of biopsy specimens and was significantly associated with storage symptom severity, particularly urinary urgency. Patients with higher inflammation scores demonstrated significantly higher OABSS and urgency subscores and lower IIEF‐5 scores. These associations remained significant after restricting analyses to untreated patients. Immunohistochemical analyses demonstrated positive correlations between histological inflammation scores and the expression of COX‐2, IL‐6, and TGF‐β, supporting inflammation‐associated activation of epithelial and stromal signaling pathways. Although ADC values did not significantly differ between inflammation groups, lower ADC values were observed in patients with moderate‐to‐severe chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) symptoms. Conclusions Histological prostatic inflammation was associated with urinary urgency and increased expression of inflammatory and fibrosis‐related mediators in benign prostate tissue. These findings support a model in which chronic inflammation promotes tissue remodeling that may contribute to urinary urgency beyond the effects of prostate enlargement.